Mizoi Mutsumi, Takabayashi Fumiyo, Nakano Masayuki, An Yan, Sagesaka Yuko, Kato Koichi, Okada Shoji, Yamanaka Kenzo
Department of Environmental Toxicology and Carcinogenesis, Nihon University College of Pharmacy, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan.
Toxicol Lett. 2005 Aug 14;158(2):87-94. doi: 10.1016/j.toxlet.2005.03.009. Epub 2005 Apr 14.
We investigated the relationship between lung- and skin-tumor promotion and oxidative stress caused by administration of dimethylarsinic acid (DMA(V)) in mice. The incidence of lung tumors induced by lung tumor initiator (4NQO) and DMA(V) were, as well as 8-oxo-2'-deoxyguanosine (8-oxodG), suppressed by cotreatment with (-)epigallocatechin gallate (EGCG). When mice were topically treated with trivalent dimethylated arsenic (DMA(III)), a further reductive metabolite of DMA(V), not only an increase in skin tumors but also an elevation of 8-oxodG in epidermis were observed. These results suggest that tumor promotion due to DMA(V) administration is mediated by DMA(III) through the induction of oxidative stress.
我们研究了小鼠体内二甲基胂酸（DMA(V)）给药所引起的氧化应激与肺和皮肤肿瘤促进之间的关系。肺肿瘤引发剂（4NQO）和DMA(V)诱导的肺肿瘤发生率以及8-氧代-2'-脱氧鸟苷（8-oxodG），均通过与（-）表没食子儿茶素没食子酸酯（EGCG）联合处理而受到抑制。当小鼠经皮给予DMA(V)的进一步还原代谢产物三价二甲基砷（DMA(III)）时，不仅观察到皮肤肿瘤增加，而且表皮中的8-oxodG水平也升高。这些结果表明，DMA(V)给药引起的肿瘤促进是由DMA(III)通过诱导氧化应激介导的。
